chr8-115764104-C-T

Position:

• chr8-115764104-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000422939.1(TRPS1):​c.-356+45529G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,132 control chromosomes in the GnomAD database, including 8,045 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (8045 hom., cov: 32)
• Consequence: TRPS1 ENST00000422939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

Genes affected

TRPS1 (HGNC:12340): (transcriptional repressor GATA binding 1) This gene encodes a transcription factor that represses GATA-regulated genes and binds to a dynein light chain protein. Binding of the encoded protein to the dynein light chain protein affects binding to GATA consensus sequences and suppresses its transcriptional activity. Defects in this gene are a cause of tricho-rhino-phalangeal syndrome (TRPS) types I-III. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPS1	ENST00000422939.1	c.-356+45529G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27450 AN: 152014 Hom.: 8010 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.00653

Gnomad OTH AF: 0.125

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.181 AC: 27544 AN: 152132 Hom.: 8045 Cov.: 32 AF XY: 0.176 AC XY: 13090 AN XY: 74374

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.00348

Gnomad4 SAS AF: 0.0332

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00653

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0605 Hom.: 843

Bravo AF: 0.205

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0010
DANN	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10505268; hg19: chr8-116776330;